Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:1.6.99.3 (diaphorase)
 5,903 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The ability of isolated adrenocortical cells to secrete corticosterone in response to ACTH challenge declines as rats age, but the site or mechanism(s) of this impairment is still unknown. To test the functionality of steroidogenic capacity per se, we measured the key enzyme activities involved in corticosterone biosynthesis. We also measured the mitochondrial cytochrome P-450 content and nonsteroidogenic enzymes specific for subcellular fractions. Mitochondria and microsomal fractions were isolated from the adrenals of 2-, 12-, and 18-month-old animals and used for various enzyme measurements. Mitochondrial side-chain cleavage enzyme activity (nanomoles per min mg protein-1) increased from a mean of 0.43 +/- 0.06 in 2-month-old rats to 1.26 +/- 0.11 and 1.51 +/- 0.06 in 12- and 18-month old rats, respectively. After incubation with 5-cholesten-3 beta,25-diol (25-hydroxycholesterol; 25 micrograms/ml) side-chain cleave activity rose to 5.0 +/- 0.6, 12.4 +/- 1.2, and 16 +/- 1.4 nmol min-1 mg protein-1 in adrenal mitochondrial fractions from 2-, 12-, and 18-month-old rats, respectively. In contrast, mitochondrial cytochrome P-450 content did not vary with advancing age. Microsomal delta 5-3 beta-hydroxysteroid dehydrogenase-delta 5-delta 4-isomerase activities were similar in 2- and 12-month-old rats, but 21-hydroxylase (nanomoles per min mg protein-1) activity was significantly increased in 12-month-old rats (2-month-old, 5.2 +/- 0.2; 12-month-old, 7.7 +/- 0.5). Finally, mitochondrial 11 beta-hydroxylase was comparable in both age groups. In addition, activities of mitochondrial nonsteroidogenic enzymes, such as monoamine oxidase, amytal insensitive NADH cytochrome c reductase, cytochrome c oxidase, succinate dehydrogenase, and malate dehydrogenase, did not change with age. It appears from the evidence presented that the activities of the steroidogenic enzymes are not responsible for the diminished capacity in corticosterone production seen with aging in the rat.
 ...
PMID:The influence of age on steroidogenic enzyme activities of the rat adrenal gland: enhanced expression of cholesterol side-chain cleavage activity. 356 41

Thirty adrenal glands from patients with adreno-leukodystrophy (ALD) have been studied by light microscopy, three by enzyme histochemistry, three by electron microscopy and two by tissue culture. Cytoplasmic ballooning and striations result from proliferation of smooth endoplasmic reticulum and accumulations of lamellar-lipid profiles and clear clefts (crystalloids). Striated adrenocortical cells, the only pathognomonic adrenal lesion in ALD, display cytoplasmic lamellae, decreased amounts of rough endoplasmic reticulum and depression of several enzymes (alpha-glycerophosphate dehydrogenase, 3 beta-hydroxysteroid dehydrogenase and TPNH diaphorase). The striated cells also demonstrate decreased ability to adapt to changes in microenvironment, both in vivo and in vitro. A blunted response by striated cells to focal peripheral cytolysis leads to cytoplasmic erosion, atrophy and macrovacuoles. ACTH has a pivotal role in the evolution of these lesions. We propose that the pathognomonic lamellae of ALD basically represent bilayers or bimolecular leaflets of very long chain saturated fatty acids, while lamellar-lipid profiles and clefts contain cholesterol esterified to these abnormal fatty acids. The similarity of lamellar-lipid profiles of ALD to cytoplasmic lesions induced by long chain saturated fatty acids suggests that the very long chain saturated fatty acids isolated in ALD are cytotoxic and are responsible for adrenocortical cell dysfunction in this disease.
 ...
PMID:A correlative study of the adrenal cortex in adreno-leukodystrophy--evidence for a fatal intoxication with very long chain saturated fatty acids. 746 18

Differential screening of an adrenal cortex cDNA library for corticotropin (ACTH)-inducible genes led to the isolation of a group of cDNAs representing mitochondrial genes that encode subunits of cytochrome oxidase, ATPase, and NADH dehydrogenase. Northern blot analysis of RNA from cells stimulated by ACTH confirmed the induction of these genes by ACTH yet revealed major differences in the relative responses of the respective mRNAs. The levels of mRNAs for cytochrome oxidase subunit I and ATPase increased 2- to 4-fold and for NADH dehydrogenase subunit 3 increased 20-fold, whereas the levels of the mitochondrial 16S rRNA showed no change within 6 h of ACTH stimulation. These effects of ACTH on mitochondrial mRNA levels probably result from both activation of the H2 transcription unit that encodes mitochondrial mRNAs and alteration of mRNA stability. ACTH also increased the activity of cytochrome oxidase after 12 h of stimulation. Examination of the tissue specificity of expression of five mitochondrial genes showed a wide range of RNA levels among 11 tissues but high correlations between individual RNA levels, consistent with a coordinated expression of the mitochondrial genes, although at different levels in each cell type. Proportionately high levels of mitochondrial mRNAs were found in adrenal cortex, probably reflecting a stimulatory effect of ACTH in vivo. Overall, the results indicate that ACTH enhances the energy-producing capacity of adrenocortical cells.
 ...
PMID:Mitochondrial-genome-encoded RNAs: differential regulation by corticotropin in bovine adrenocortical cells. 750 67